Animal Models of Addiction

摘要： 人们普遍认为，有限的(短通道，Sa)可卡因自我给药经验 不会在大脑和与上瘾相关的行为方面产生变化。使用最广泛的 成瘾模型包括长时间的访问程序(LGA，6小时+/天)，这会大大增加 药物消耗量。LGA会产生一些类似成瘾的行为，并且 脑部的变化，不能见于沙氏。然而，除了可卡因的使用量之外， 使用的时间模式--它的间歇性--在产生类似成瘾的过程中也很重要 行为和相关的神经适应。Zimmer等人。(2013)开发了一种间歇性 访问自我给药程序(INTA)以更好地模拟可卡因的间歇模式 在瘾君子身上看到的用法。他发现，尽管药物总消耗量要少得多，但动机 有INTA经验的大鼠的可卡因含量高于有LGA经验的大鼠。一致 有了这一点，我们发现INTA产生了强大的激励敏感化，正如一个 可卡因需求逐步增加(基于行为经济指标)，以及 相关的摄入量增加，以及非常强劲的可卡因寻觅行为的恢复- 尽管消耗的药物比LGA条件下的要少得多。因此，我们的总体目标是直接 比较和对比这两者对行为、心理和神经生物学的影响 上瘾的模特儿。总体目标是确定大脑和行为的变化 LGA与INTA产生的经验只有数量上的不同，或者说，是否有定性的 结果上的差异。这些信息将对做出有关 动物模型用于成瘾的临床前研究，也将在确定 治疗学发展的方向。

Abstract: It is generally accepted that limited (Short Access, ShA) cocaine self-administration experience does not produce changes in brain and behavior associated with addiction. The most widely used models of addiction involve Long Access procedures (LgA, 6hrs+/day), which greatly increase the amount of drug consumption. LgA produces a number of addiction-like behaviors, and changes in brain, not seen with ShA. However, in addition to the amount of cocaine use, the temporal pattern of use – how intermittent it is – is also important in producing addiction-like behavior and associated neuroadaptations. Zimmer et al. (2013) developed an intermittent access self-administration procedure (IntA) to better model the intermittent patterns of cocaine use seen in addicts. He found that, despite much less total drug consumption, motivation for cocaine was higher in rats with prior IntA experience than those with LgA experience. Consistent with this, we found that IntA produces robust incentive-sensitization, as indicated by a progressive increase in cocaine demand (based on behavioral economic indicators), an associated escalation of intake, and very robust reinstatement of cocaine seeking behavior – despite consuming much less drug than under LgA conditions. Thus, our Overall Aim is to directly compare and contrast the behavioral, psychological and neurobiological effects of these two models of addiction. The overall goal is to determine whether the changes in brain and behavior produced by LgA vs. IntA experience only differ quantitatively, or, whether there are qualitative differences in outcomes. This information will be critical in making informed decisions about the animal model to use in preclinical studies of addiction, and will also be important in determining directions in the development of therapeutics.